4.6 Article

Chronic exposure to innocuous leads to suppressed airway antigen in sensitized mice eosinophilia that is reversed by granulocyte macrophage colony-stimulating factor

Journal

JOURNAL OF IMMUNOLOGY
Volume 169, Issue 7, Pages 3499-3506

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.169.7.3499

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In this study we investigated the impact of chronic allergen exposure on airway inflammation and Immoral responses in sensitized mice. We observed marked eosinophilia in the bronchoalveolar lavage, lung tissue, and peripheral blood after 2 wk of exposure. In contrast, eosinophilia was markedly reduced by 3 wk and completely resolved by 4 wk of exposure, despite the continued presence of Ag. Decreases in airway eosinophilia were associated with a robust Immoral response. We observed that levels of OVA-specific IgE, IgG1, and IgG2a increased during the course of exposure. To assess whether continuous exposure to Ag impacts the ability of the lung to respond to subsequent Ag challenge, mice were exposed to either 2 or 4 wk of OVA in the context of GM-CSF. All groups were then rested for 28 days and exposed to OVA on three consecutive days. We observed a significant decrease in airway eosinophilia and IL-5 expression in the bronchoalveolar lavage and serum in mice initially exposed to 4 wk of OVA, compared with animals exposed to 2 wk only. However, in both groups expression of B7.2 on dendritic cells as well as CD25, CD69, and T1/ST2 on CD4(+) T cells was enhanced, suggesting immune activation. Delivery of rGM-CSF fully restored airway eosinophilia. This study shows that exposure to innocuous Ag alone does not lead, to persistent eosinophilic airway inflammation, but rather to abrogated eosinophilia. This suppression can be reversed by GM-CSF.

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